Determining the target of membrane sterols on voltage-gated potassium channels

Abstract

Determining the target of membrane sterols on voltage-gated potassium channels. Bbamcb (2018),

An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin

“…Due to the mostly non-uniform charge distribution of proteins, the immense DP-associated electric field can be essential in the regulation of the conformational stability and consequently the functional activity of membrane proteins (O'Shea, 2003;Richens et al, 2015;Zakany et al, 2020). Consistently, DP was suggested to influence the function of bacterial ionophores (Ostroumova et al, 2012), voltage-gated ion channels (Pearlstein et al, 2017;Zakany et al, 2019), Na + /K + ATPase (Clarke, 2015), P-glycoprotein (Davis et al, 2015) serotonin receptors (Bandari et al, 2014) and ErbB proteins (Kovacs et al, 2016). The DP can also modify membrane binding of drugs (Asawakarn et al, 2001), β-amyloid (Hertel et al, 1997) and other peptides (Cladera and O'Shea, 1998;Zhan and Lazaridis, 2012).…”

Statin‐boosted cellular uptake and endosomal escape of penetratin due to reduced membrane dipole potential

“…Because the electric field associated with the dipole potential is confined to the surface of the membrane, its strength is 10 8 -10 9 V/m, larger by 1-2 orders of magnitude than the field associated with the transmembrane potential. Therefore, the dipole potential exerts significant effects on the conformation of transmembrane proteins (Clarke, 2015;Kov acs et al, 2016;Z ak any et al, 2019, on the binding of molecules to the membrane (Cladera & O'Shea, 1998) and their transmembrane transport (Flewelling & Hubbell, 1986). One of the most important factors determining the dipole potential is the sterol content of membranes.…”

Interfacial Binding Sites for Cholesterol on Kir, Kv, K2P, and Related Potassium Channels

“…Kir channel activity generally decreases with increasing cholesterol content but sometimes increases (3,4,7,8), with effects being due to a shift between active and silent states (9) or to changes in open probability (7,8,10). Effects of cholesterol on Kv channel function have proved rather controversial (11,12) and could follow from changes in single-channel conductance rather than from changes in open probability (13) or from effects on the stability of the open state (14). In-creases in cholesterol content have been reported to decrease the open probability of the Slo1 (BK) channel (6).…”